Fevers in man and rabbits appear to be due to the release into the blood stream of a pyrogenic protein which can be produced by certain cells of the reticuloendothelial system. This research project is concerned with characterization of the pyrogenic protein released by the liver and spleen and with investigation of the mechanism of production of the pyrogen by the cell. As a result of these studies, we hope to be able to define the conditions both in vitro and in vivo under which each cell type releases pyrogen. These studies should provide a more complete understanding of the role of the reticuloendothelial system in the pathogenesis of fever.